Method and apparatus for neural stimulation via the lymphatic system

ABSTRACT

An implantable neural stimulation system includes an implantable medical device having a neural stimulation circuit and at least one implantable lead configured to allow one or more stimulation electrodes to be placed in one or more lymphatic vessels of a patient, such as the patient&#39;s thoracic duct and/or vessels branching from the thoracic duct. Neural stimulation pulses are delivered from the implantable medical device to one or more target regions adjacent to the thoracic duct or the vessels branching from the thoracic duct through the one or more stimulation electrodes.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is related to co-pending, commonly assigned, U.S.patent application Ser. No. ______, entitled “METHOD AND APPARATUS FORLYMPHATIC SYSTEM PACING AND SENSING,” filed on even date herewith(Attorney Docket No. 279.A69US1), U.S. patent application Ser. No.______, entitled “METHOD AND APPARATUS FOR GASTROINTESTINAL STIMULATIONVIA THE LYMPHATIC SYSTEM,” filed on even date herewith ______ (AttorneyDocket No. 279.A66US1), U.S. patent application Ser. No. ______,entitled “METHOD AND DEVICE FOR LYMPHATIC SYSTEM MONITORING,” filed evendate herewith (Attorney Docket No. 279.A05US1), and U.S. patentapplication Ser. No. ______, entitled “METHOD AND DEVICE FORENDO-LYMPHATIC STIMULATION,” filed on even date herewith (AttorneyDocket No. 279.A04US1), which are hereby incorporated herein byreference in their entirety.

TECHNICAL FIELD

This document relates generally to medical devices and particularly toan implantable system that delivers neural stimulation via one or morelymphatic vessels.

BACKGROUND

Neural stimulation has been applied to treat various pathologicalconditions. Controlled delivery of electrical stimulation pulses to anerve generates, modulates, or inhibits activities of that nerve,thereby restoring the functions of that nerve and/or regulating thefunctions of the tissue or organ innervated by that nerve. One specificexample of neural stimulation is to regulate cardiac functions andhemodynamic performance by delivering electrical stimulation pulses toportions of the autonomic nervous system. The heart is innervated withsympathetic and parasympathetic nerves. Activities in these nerves,including artificially applied electrical stimuli, modulate cardiacfunctions and hemodynamic performance. Direct electrical stimulation ofparasympathetic nerves can activate the baroreflex, inducing a reductionof sympathetic nerve activity and reducing blood pressure by decreasingvascular resistance. Sympathetic inhibition, as well as parasympatheticactivation, has been associated with reduced arrhythmia vulnerabilityfollowing a myocardial infarction, presumably by increasing collateralperfusion of the acutely ischemic myocardium and decreasing myocardialdamage. Modulation of the sympathetic and parasympathetic nervous systemwith neural stimulation has been shown to have positive clinicalbenefits, such as protecting the myocardium from further remodeling andpredisposition to fatal arrhythmias following a myocardial infarction.

Implantable medical systems are used to deliver neural stimulation. Atypical implantable neural stimulation system includes an implantableneural stimulator that delivers electrical stimulation pulses through aplurality of stimulation electrodes. Depending on the location of thenerve to be stimulated, the stimulation electrodes may be incorporatedonto the implantable neural stimulator and/or connected to theimplantable neural stimulator using one or more implantable leads. Inpractice, the desirable stimulation sites may not be in a location withanatomical structure allowing for easy implantation of the implantableneural stimulator or easy access by the lead(s). The degree of riskassociated with the implantation procedure increases with the degree ofinvasiveness. Therefore, given a desirable stimulation site, there is aneed to minimize the invasiveness of implanting a system that deliversneural stimulation pulses to that stimulation site.

SUMMARY

An implantable neural stimulation system includes an implantable medicaldevice having a neural stimulation circuit and at least one implantablelead configured to allow one or more stimulation electrodes to be placedin one or more lymphatic vessels of a patient, such as the patient'sthoracic duct and/or vessels branching from the thoracic duct. Neuralstimulation pulses are delivered from the implantable medical device toone or more target regions adjacent to the thoracic duct or the vesselsbranching from the thoracic duct through the one or more stimulationelectrodes.

In one embodiment, a neural stimulation system includes an electrodeassembly and an implantable medical device. The electrode assemblyincludes an electrode base configured to be implanted into a lymphaticvessel and a stimulation electrode on the electrode base. The electrodebase is configured to cause a portion of the lymphatic vessel tosubstantially alter its natural path to contact a target region to whichneural stimulation pulses are delivered and maintain the contact betweenthe portion of the lymphatic vessel and the target region after theimplantation of the electrode assembly. The implantable medical deviceincludes a neural stimulation circuit that delivers the neuralstimulation pulses through the stimulation electrode.

In one embodiment, a method for delivering neural stimulation isprovided. Neural stimulation pulses are delivered from an implantablemedical device to at least one stimulation electrode placed in alymphatic vessel.

This Summary is an overview of some of the teachings of the presentapplication and not intended to be an exclusive or exhaustive treatmentof the present subject matter. Further details about the present subjectmatter are found in the detailed description and appended claims. Otheraspects of the invention will be apparent to persons skilled in the artupon reading and understanding the following detailed description andviewing the drawings that form a part thereof. The scope of the presentinvention is defined by the appended claims and their legal equivalents.

BRIEF DESCRIPTION OF THE DRAWINGS

The drawings illustrate generally, by way of example, variousembodiments discussed in the present document. The drawings are forillustrative purposes only and may not be to scale.

FIG. 1 is an illustration of an embodiment of a neural stimulationsystem and portions of an environment in which the neural stimulationsystem is used.

FIG. 2 is an illustration of another embodiment of the neuralstimulation system and portions of the environment in which the neuralstimulation system is used.

FIG. 3 is a block diagram illustrating an embodiment of an implantablemedical device of the neural stimulation system.

FIG. 4 is a block diagram illustrating a specific embodiment of theimplantable medical device.

FIG. 5 is a block diagram illustrating another specific embodiment ofthe implantable medical device.

FIG. 6 is a block diagram illustrating an embodiment of an externalsystem of the neural stimulation system.

FIG. 7 is a block diagram illustrating an embodiment of the externalsystem being a patient management system.

FIG. 8 is a flow chart illustrating a method for delivering neuralstimulation via the thoracic duct.

FIG. 9 is an illustration of a lymphatic vessel and a target region forneural stimulation.

FIG. 10 is an illustration of an embodiment of an electrode assembly forplacement in the lymphatic vessel to allow for the neural stimulation.

FIG. 11 is an illustration of an embodiment of another electrodeassembly for placement in the lymphatic vessel to allow for the neuralstimulation.

FIG. 12 is an illustration of an embodiment of another electrodeassembly for placement in the lymphatic vessel to allow for the neuralstimulation.

FIG. 13 is an illustration of an embodiment of another electrodeassembly for placement in the lymphatic vessel to allow for the neuralstimulation.

DETAILED DESCRIPTION

In the following detailed description, reference is made to theaccompanying drawings which form a part hereof, and in which is shown byway of illustration specific embodiments in which the invention may bepracticed. These embodiments are described in sufficient detail toenable those skilled in the art to practice the invention, and it is tobe understood that the embodiments may be combined, or that otherembodiments may be utilized and that structural, logical and electricalchanges may be made without departing from the spirit and scope of thepresent invention. References to “an”, “one”, or “various” embodimentsin this disclosure are not necessarily to the same embodiment, and suchreferences contemplate more than one embodiment. The following detaileddescription provides examples, and the scope of the present invention isdefined by the appended claims and their legal equivalents.

This document discusses an implantable neural stimulation systemincluding an implantable medical device delivering neural stimulationthrough at least one stimulation delivery device placed in a lymphaticvessel, such as the thoracic duct, of a patient. In one embodiment, theimplantable neural stimulation system includes a transluminal leadconfigured for insertion into a portion of the lymphatic vessel to allowone or more stimulation electrodes to be placed in the lymphatic vessel.The implantable medical device includes a neural stimulation circuitthat generates electrical pulses. The electrical pulses are delivered toone or more target regions adjacent to the lymphatic vessel through theone or more stimulation electrodes placed in the lymphatic vessel. Whilethe thoracic duct is specifically discussed in this document as anexample of such a lymphatic vessel, neural stimulation pulses aredelivered through any one or more lymphatic vessels, including, but notlimited to, the thoracic duct, lymphatic vessels branching from thethoracic duct, the right lymphatic duct, and lymphatic vessels branchingfrom the right lymphatic duct.

While electrical stimulation is specifically discussed in this documentas an example, the present subject matter includes neurostimulationusing any form of energy that is capable of stimulating one or morecomponents of the nervous system via the lymphatic vessel such as thethoracic duct. In various embodiments, the stimulation delivery deviceplaced in the lymphatic vessel generates or receives neural stimuli,which are then delivered to one or more neural stimulation sites via thelymphatic vessel. The neural stimuli are in one or more forms of energythat are capable of eliciting a neural response, such as electrical,magnetic, electromagnetic, thermal, and/or acoustic (includingultrasonic) energy.

FIG. 1 is an illustration of an embodiment of a neural stimulationsystem 100 and portions of an environment in which system 100 is used.System 100 includes an implantable medical device 110, a lead 112, anexternal system 130, and a telemetry link 125 providing forcommunication between implantable medical device 110 and external system130.

System 100 delivers neural stimulation pulses through at least oneelectrode placed in a thoracic duct 105, which is part of the lymphaticsystem of a patient's body 101. The lymphatic system includes lymphtissue, nodes, and vessels. Interstitial fluid is absorbed from tissue,filtered through lymph nodes, and empties into lymphatic vessels. FIG. 1illustrates portions of thoracic duct 105, a subclavian vein 102, a leftexternal jugular vein 104, a left internal jugular vein 103, and asuperior vena cava 106. Thoracic duct 105 connects to the venous systemat the juncture of subclavian vein 102 and a left internal jugular vein103. The fluid (lymph) from the lower body flows up to thoracic duct 105and empties into subclavian vein 102 from thoracic duct 105. Thoracicduct 105 is located in the posterior mediastinal area of body 101,adjacent to the heart and various portions of the nervous systemincluding portions of the vagus, sympathetic, and phrenic nerves.Electrical stimulation of such nerves is delivered by using one or morestimulation electrodes placed within thoracic duct 105. Thoracic duct105 is used as a conduit for advancing the one or more stimulationelectrodes to a location from which electrical stimulation can bedelivered to a target region of the nervous system of body 101. Thisapproach to the process of electrode placement for neural stimulationhas the potential of reducing the invasiveness of implantation procedureunder many circumstances.

Implantable medical device 110 generates neural stimulation pulses thatare electrical pulses and delivers the neural stimulation pulses throughlead 112. In one embodiment, implantable medical device 110 also sensesneural activities using at least lead 112. In various embodiments,implantable medical device 110 is capable of sensing other physiologicalsignals and/or delivering therapies in addition to the neuralstimulation. Examples of such additional therapies include cardiacpacing therapy, cardioversion/defibrillation therapy, cardiacresynchronization therapy (CRT), cardiac remodeling control therapy(RCT), drug therapy, cell therapy, and gene therapy. In variousembodiments, implantable medical device 110 delivers the neuralstimulation in coordination with one or more such additional therapies.In one embodiment, in addition to lead 112, system 100 includes one ormore endocardial and/or epicardial leads for delivering pacing and/ordefibrillation pulses to the heart.

Lead 112 is an implantable neural stimulation lead including a proximalend 114, a distal end 116, and an elongate lead body 118 betweenproximal end 114 and distal end 116. Proximal end 114 is coupled toimplantable medical device 110. Distal end 116 includes at least onestimulation electrode for delivering the neural stimulation pulses to atarget region of the nervous system of body 101. In one embodiment, asillustrated in FIG. 1, distal end 116 includes stimulation electrodes120 and 122. In various other embodiments, distal end 116 includes onestimulation electrode or three or more stimulation electrodes. In oneembodiment, a reference electrode is incorporated onto implantablemedical device 110. In a specific embodiment, implantable medical device110 includes a hermetically sealed conductive housing that functions asthe reference electrode. Neural stimulation pulses are delivered using(i) two stimulation electrodes in distal end 116 (electrodes 120 or122), or (ii) a stimulation electrode (electrode 120 or 122) in distalend 116 and the reference electrode on implantable medical device 110.In various embodiments, one or more of the stimulation electrodes arealso used for sensing one or more neural signals. The distal portion ofelongate lead body 118 (a substantial portion of elongate lead body 118coupled to distal end 116) is configured for placement in subclavianvein 102 and thoracic duct 105, such that distal end 116 is placed inthoracic duct 105. During the implantation of lead 112, distal end 116is inserted into subclavian vein 102 through an incision, advanced insubclavian vein 102 toward thoracic duct 105, inserted into thoracicduct 105 from subclavian vein 102, and advanced in thoracic duct 105until a predetermined location in thoracic duct 105 is reached. In oneembodiment, the position of distal end 116 is adjusted by deliveringtest neural stimulation pulses and detecting evoked neural signalsand/or other physiological responses. In one embodiment, lead 112includes a fixation mechanism configured to stabilize distal end 116 inthe determined position in thoracic duct 105. Implantable medical device110 is connected to proximal end 114 and is subcutaneously implanted.One example of method and apparatus for accessing the lymphatic systemis discussed in U.S. patent application Ser. No., ______, entitled“METHOD AND APPARATUS FOR LYMPHATIC SYSTEM PACING AND SENSING,” filed oneven date herewith (Attorney Docket No. 279.A69 μl), assigned to CardiacPacemakers, Inc., which is incorporated herein by reference in itsentirety. Specific examples of electrode configurations and placementare also discussed in detail below, with reference to FIGS. 9-12.

In one embodiment, lead 112 is configured such that distal end 116 canbe further advanced into a lymphatic vessel branching from thoracic duct105, such as the gastric branch, so that the stimulation electrode canbe placed in close proximity of a desirable target region. After thedistal end 116 is inserted into thoracic duct 105, it is advanced to thejunction of thoracic duct 105 and the branching lymphatic vessel andinserted to the branching lymphatic vessel. While the placement of atleast one stimulation electrode in the thoracic duct is specificallydiscussed as an example of providing for access to a target region, thepresent subject matter generally includes introducing one or morestimulus delivery devices such as one or more stimulation electrodes toa stimulation site via a lymphatic vessel. In various embodiments,neural stimulation pulses are delivered through one or more stimulationelectrodes placed in the lymphatic vessel and/or one or more stimulationelectrodes placed in a structure that is accessible through thelymphatic vessel, including another lymphatic vessel branching from thelymphatic vessel.

In one embodiment, system 100 includes two or more leads each includingone or more stimulation electrodes arranged to be placed in thoracicduct 105. In another embodiment, a lead includes a plurality ofelectrodes arranged for delivering independently controllable neuralstimulation pulses to two or more target regions.

External system 130 communicates with implantable medical device 110 andprovides for access to implantable medical device 110 by a physician orother caregiver. In one embodiment, external system 130 includes aprogrammer. In another embodiment, external system 130 is a patientmanagement system including an external device communicating withimplantable medical device 110 via telemetry link 125, a remote devicein a relatively distant location, and a telecommunication networklinking the external device and the remote device. The patientmanagement system allows access to implantable medical device 110 from aremote location, for purposes such as monitoring patient status andadjusting therapies. In one embodiment, telemetry link 125 is aninductive telemetry link. In another embodiment, telemetry link 125 is afar-field radio-frequency (RF) telemetry link. Telemetry link 125provides for data transmission from implantable medical device 110 toexternal system 130. This includes, for example, transmitting real-timephysiological data acquired by implantable medical device 110,extracting physiological data acquired by and stored in implantablemedical device 110, extracting patient history data such as occurrencesof predetermined types of pathological events and therapy deliveriesrecorded in implantable medical device 110, and/or extracting dataindicating an operational status of implantable medical device 110(e.g., battery status and lead impedance). Telemetry link 125 alsoprovides for data transmission from external system 130 to implantablemedical device 110. This includes, for example, programming implantablemedical device 110 to acquire physiological data, programmingimplantable medical device 110 to perform at least one self-diagnostictest (such as for a device operational status), and/or programmingimplantable medical device 110 to deliver one or more therapies and/orto adjust the delivery of one or more therapies.

FIG. 2 is an illustration of an embodiment of a neural stimulationsystem 200 and portions of the environment in which system 200 is used.System 200 includes the components of neural stimulation system 100 andan additional lead. That is, neural stimulation system 200 includesimplantable medical device 110, leads 112 and 232, external system 130,and telemetry link 125.

Lead 232 is an implantable neural stimulation lead including a proximalend 234, a distal end 236, and an elongate lead body 238 betweenproximal end 234 and distal end 236. Proximal end 234 is coupled toimplantable medical device 110. Distal end 236 includes at least oneelectrode. In one embodiment, as illustrated in FIG. 2, lead 232includes an electrode 240 at distal end 236. In another embodiment, lead232 includes a plurality of stimulation electrodes. In one embodiment,lead 232 is configured for subcutaneous placement, external to thoracicduct 105. In one embodiment, electrode 240 is used as a referenceelectrode.

Lead 232 expands the range of target regions to which neural stimulationpulses can be delivered from implantable medical device 110. In variousembodiments, neural stimulation pulses are delivered through any pair ofelectrodes of system 200 including (i) two stimulation electrodes indistal end 116 (electrodes 120 and 122), (ii) a stimulation electrode indistal end 116 (electrode 120 or 122) and electrode 240 (as thereference electrode), or (iii) a stimulation electrode in distal end 116(electrode 120 or 122) and the reference electrode on implantablemedical device 110. In one embodiment, distal ends 116 and 236 arepositioned such as a target structure for the neural stimulation isapproximately between a stimulation electrode in distal end 116(electrode 120 or 122) and a reference electrode (electrode 240 or thereference electrode on implantable medical device 110). For example, thetarget structure is a portion of the spinal cord of body 101.

FIG. 3 is a block diagram illustrating an embodiment of an implantablemedical device 310, which is a specific embodiment of implantablemedical device 110. Implantable medical device 310 includes a neuralstimulation circuit 346 and an implant control circuit 348. Neuralstimulation circuit 346 delivers neural stimulation pulses to a pair ofstimulation electrodes 342 and 344, through which the neural stimulationpulses are delivered to a target region in the nervous system. At leastone of stimulation electrodes 342 and 344 is placed in thoracic duct105. Implant control circuit 348 controls the delivery of the neuralstimulation pulses from neural stimulation circuit 346.

In one embodiment, stimulation electrodes 342 and 344 are both inthoracic duct 105 and adjacent to the target region, such as electrodes120 and 122. In another embodiment, stimulation electrode 342 is inthoracic duct 105 and adjacent to the target region, such as electrode120 or 122, and stimulation electrode 344 is external to thoracic duct105, such as electrode 240 or a reference electrode on implantablemedical device 310. In one embodiment, the target region isapproximately between stimulation electrodes 342 and 344.

In various embodiments, the target region includes one or morecomponents of the nervous system that are adjacent to the thoracic ductin the posterior mediastinal region or abdominal region. Examples of thetarget region include the sympathetic nerves, the parasympathetic nerves(including the vagus nerve), the phrenic nerve, the spinal cord, thebrain stem, the renal nerves, and the baroreceptors in the carotidartery and aorta. In one embodiment, cardiac functions are regulated byapplying neural stimulation including one or more of sympatheticexcitation, sympathetic inhibition, parasympathetic excitation, andparasympathetic inhibition. One example of a system capable of providingexcitatory stimulation and inhibitory stimulation to both sympatheticnerves and parasympathetic nerves is discussed in U.S. patentapplication Ser. No. 11/124,791, entitled “METHOD AND APPARATUS FORCONTROLLING AUTONOMIC BALANCE USING NEURAL STIMULATION,” filed on May 9,2005, assigned to Cardiac Pacemakers, Inc., which is incorporated hereinby reference in its entirety.

For illustration purposes, FIG. 3 shows the pair of stimulationelectrodes 342 and 344. In various embodiments, neural stimulationcircuit 346 delivers neural stimulation pulses through one or more pairsof stimulation electrodes selected from a plurality of stimulationelectrodes. In one embodiment, neural stimulation circuit 346 includestwo or more stimulation output channels each delivering neuralstimulation pulses through a pair of stimulation electrodes. In anotherembodiment, an electrode array with a plurality of stimulationelectrodes is placed in the thoracic duct, and one or more stimulationelectrodes are selected for delivering neural stimulation pulses bytesting the physiological effect of stimulation associated with eachstimulation electrode.

FIG. 4 is a block diagram illustrating an embodiment of an implantablemedical device 410, which is another specific embodiment of implantablemedical device 110. Implantable medical device 410 includes neuralstimulation circuit 346, a sensing circuit 452, an implant controlcircuit 448, and an implant telemetry circuit 458. One or morephysiological sensors 450 are housed within implantable medical device410, incorporated onto implantable medical device 410, and/or connectedto implantable medical device 410 using a lead.

Physiological sensor(s) 450 sense one or more physiological signalsindicative of neural function and/or physiological functions regulatedby the components of the nervous system to be stimulated. Sensingcircuit 452 processes the one or more physiological signals and producessignals indicative of a need to start, stop, or adjust the neuralstimulation. Examples of such physiological signals include signalsindicative of heart rate, heart rate variability (HRV), and bloodpressure. In one embodiment, physiological sensor(s) 450 include one orboth of stimulation electrodes 342 and 344, which are utilized assensing electrodes.

Implant control circuit 448 is a specific embodiment of implant controlcircuit 348 and controls the delivery of the neural stimulation pulsesfrom neural stimulation circuit 346 using a plurality of stimulationparameters. Implant control circuit 448 includes a parameter storagecircuit 454 and a parameter receiver 456. Parameter storage circuit 454stores values of the plurality of stimulation parameters. Examples ofsuch stimulation parameters include pulse amplitude, pulse width, andpulse frequency (or inter-pulse interval). The values of the pluralityof stimulation parameters are adjustable. Parameter receiver 456receives values of the plurality of stimulation parameters and updatesparameter storage circuit 454 with the received values. In oneembodiment, implant control circuit 448 controls the delivery of theneural stimulation pulses from neural stimulation circuit 346 using oneor more physiological signals sensed by physiological sensor(s) 450. Invarious embodiments, each sensed physiological signal is used as one ormore of a triggering signal to start or stop the neural stimulation, asafety assurance signal to start, stop, or adjust the intensity of theneural stimulation, and a feedback signal to provide closed-loop neuralstimulation.

Implant telemetry circuit 458 transmits and receives data via telemetrylink 125. In one embodiment, the values of the plurality of stimulationparameters are externally programmable, and the programmed values arereceived from external system 130 through telemetry link 125.

FIG. 5 is a block diagram illustrating an implantable medical device510, which is a specific embodiment of implantable medical device 410.Implantable medical device 510 includes neural stimulation circuit 346,a neural sensing circuit 552, an implant control circuit 548, andimplant telemetry circuit 458.

Neural sensing circuit 552 is a specific embodiment of sensing circuit452 and processes a neural signal sensed using neural sensing electrodes562 and 564, which represent a specific embodiment of physiologicalsensor(s) 450. In one embodiment, neural sensing circuit 552 processestwo or more neural signals sensed using additional neural sensingelectrodes. In one embodiment, the neural signal is sensed from the samesite to which the neural stimulation pulses are delivered, andstimulation electrodes 342 and 344 are used as neural sensing electrodes562 and 564. In other words, stimulation electrodes 342 and 344 andneural sensing electrodes 562 and 564 are physically the same pair ofelectrodes. In another embodiment, the neural signal is sensed from asite different from the site to which the neural stimulation pulses aredelivered. At least one of stimulation electrodes 342 and 344 is notused as any of neural sensing electrodes 562 and 564.

Implant control circuit 548 is a specific embodiment of implant controlcircuit 448 and includes a closed-loop controller 560, parameter storagecircuit 454, and parameter receiver 456. Implant control circuit 548controls the delivery of the neural stimulation pulses from neuralstimulation circuit 346 using a plurality of stimulation parameters andthe sensed and processed neural signal. Closed-loop controller 560controls the delivery of the neural stimulation pulses using the sensedand processed neural signal as an input for feedback control. Examplesof closed-loop neural stimulation are discussed in U.S. patentapplication Ser. No. 11/280,940, entitled “SYSTEM AND METHOD FORCLOSED-LOOP NEURAL STIMULATION,” filed on Nov. 16, 2005, assigned toCardiac Pacemakers, Inc., which is incorporated herein by reference inits entirety.

FIG. 6 is a block diagram illustrating an embodiment of an externalsystem 630, which is a specific embodiment of external system 130.External system 630 includes an external telemetry circuit 670, anexternal controller 672, and a user interface 674. External telemetrycircuit 670 transmits and receives data via telemetry link 125. Externalcontroller 672 controls the operation of external system 630. Userinterface 674 allows a user such as a physician or other caregiver tocommunicate with implantable medical device 110 through external system630. User interface 674 includes a presentation device 676 and a userinput device 678. User input device 678 allows for the programming ofthe values of the plurality of stimulation parameters. In oneembodiment, presentation device 676 and user input device 678 areintegrated or partially integrated to include an interactive screenallowing for programming of implantable medical device 110.

In one embodiment, external system 630 includes a programmer. In anotherembodiment, external system 630 includes a patient management system asdiscussed below with reference to FIG. 7.

FIG. 7 a block diagram illustrating an embodiment of an external system730, which is a specific embodiment of external system 630. Asillustrated in FIG. 7, external system 730 is a patient managementsystem including an external device 780, a telecommunication network782, and a remote device 784. External device 780 is placed within thevicinity of implantable medical device 110 and includes externaltelemetry system 670 to communicate with the implantable medical devicevia telemetry link 125. Remote device 784 is in a remote location andcommunicates with external device 780 through network 782. Remote device784 includes user interface 674 to allow the physician or othercaregiver to monitor and treat a patient from a distant location and/orallowing access to various treatment resources from the remote location.

FIG. 8 is a flow chart illustrating a method for delivering neuralstimulation via the thoracic duct. In one embodiment, the method isperformed using system 100 or system 200, including the variousembodiments of their components discussed above.

A neural stimulation lead is inserted into a lymphatic vessel of apatient at 800. In one embodiment, this lymphatic vessel is the thoracicduct. The neural stimulation lead is an implantable transluminal leadhaving a proximal end configured for connection to an implantablemedical device and a distal end including one or more stimulationelectrodes. To insert the neural stimulation lead into the thoracic ductsuch that neural stimulation pulses can be delivered through thestimulation electrode(s), an opening is made on the subclavian vein,upstream from the junction of the subclavian vein and the ostium of thethoracic duct. The distal end of the neural stimulation lead is insertedinto the subclavian vein through the opening and advanced toward thejunction of the subclavian vein and the ostium of the thoracic ductdownstream. Then, the neural stimulation lead is guided into thethoracic duct and advanced in the thoracic duct until the distal endreaches a region determined by the target to which the neuralstimulation pulses are delivered. Examples of the target region includeany nerve of other components of the nervous system in the mediastinalor abdominal region, adjacent to the thoracic duct, such as sympatheticnerves, parasympathetic nerves including the vagus nerve, the phrenicnerve, renal nerves, the spinal cord, the brain stem, and baroreceptorsin the carotid artery and aorta. In one embodiment, to further approacha desirable target region, the distal end of the neural stimulation leadis guided into a lymphatic vessel branching from the thoracic duct.

The stimulation electrode(s) of the neural stimulation lead arepositioned in the lymphatic vessel, such as the thoracic duct or thelymphatic vessel branching from the thoracic duct, at 810. In oneembodiment, after the distal end of the neural stimulation lead reachesthe region determined by the target, test neural stimulation pulses aredelivered. The distal end is moved in the thoracic duct or the lymphaticvessel branching from the thoracic duct until it reaches a positionidentified by detecting satisfactory responses to the stimulation, suchas evoked neural signals and/or other anticipated physiological effects.The distal end with the stimulation electrode(s) is then stabilized inthat position. In another embodiment, the neural stimulation leadincludes a plurality of stimulation electrodes. After the neuralstimulation lead is inserted, test neural stimulation pulses aredelivered to different stimulation electrodes or different combinationsof the stimulation electrodes, one at a time. A stimulation electrode ora combination of stimulation electrodes is identified for an intendedtherapy based on the responses to the stimulation, such as evoked neuralsignals and/or other anticipated physiological effects.

One or more physiological signals are sensed at 820. In one embodiment,at least one physiological signal is sensed to indicate a need to start,stop, or adjust the delivery of the neural stimulation. In anotherembodiment, at least one physiological signal is sensed for monitoring,diagnostic, and/or therapeutic purposes other then the neuralstimulation. In one embodiment, one or more neural signals are sensed.In a specific embodiment, a neural signal is sensed from the nerve towhich the neural stimulation is delivered. In another embodiment, one ormore signals each indicative of a physiological function regulated bythe stimulated nerve are sensed.

Neural stimulation pulses are delivered using the stimulationelectrode(s) positioned in the lymphatic vessel, such as the thoracicduct or the lymphatic vessel branching from the thoracic duct, at 830.In one embodiment, the neural stimulation pulses are delivered throughtwo stimulation electrodes positioned in the thoracic duct or thelymphatic vessel branching from the thoracic duct. In anotherembodiment, the neural stimulation pulses are delivered using astimulation electrode positioned in the thoracic duct or the lymphaticvessel branching from the thoracic duct and another stimulationelectrode positioned in a location in the body external to the lymphaticvessels. In a specific embodiment, the neural stimulation pulses aredelivered to a portion of the nervous system approximately between apair of stimulation electrodes. The delivery of the neural stimulationpulses is controlled using a plurality of stimulation parameters.Examples of the stimulation parameters include pulse amplitude, pulsewidth, and pulse frequency (or inter-pulse interval). These stimulationparameters are adjustable. In one embodiment, a user such as a physicianor other caregiver programs one or more values of the plurality ofstimulation parameters. In one embodiment, the delivery of the neuralstimulation pulses are also controlled using the one or morephysiological signals, including the one or more neural signals.

The neural stimulation pulses are delivered via the thoracic duct or thelymphatic vessel branching from the thoracic duct to treat one or moreclinical conditions each associated with a physiological functionregulated by a nerve or other component of the nervous system that isadjacent the thoracic duct or the lymphatic vessel branching from thethoracic duct. Examples of such clinical conditions include respiratorydisorders, abnormal blood pressure, cardiac arrhythmias, myocardialinfarction or ischemic insult (angina), heart failure, epilepsy,depression, renal disorders, pain, migraine, obesity, movementdisorders, and incontinence. Specific examples of the treatment include(i) treatment of hypertension by baroreceptor stimulation, (ii)treatment of heart failure by sympathetic inhibition or vagalexcitation; (iii) control of post-myocardial infarction remodeling bysympathetic inhibition or vagal excitation, (iv) mitigation of chronicpain by neural activation or blocking, (v) treatment of vascular painincluding refractory angina and peripheral vascular diseases (PVD) byspinal cord stimulation, (vi) treatment of rachidian pain includingfailed back surgery syndrome (FBSS), degenerative low back leg pain(LBLP), nerve root lesions, incomplete spine lesions and spinal stenosisby spinal cord stimulation, (vii) treatment of type 1 or type 2 chronicregional pain syndrome (CRPS) by spinal cord stimulation, and (viii)treatment of perineal pain and urological diseases by spinal cordstimulation, and restoration of lower extremity motor functions such asstanding and walking after spinal cord injury by ventral spinal cordstimulation.

FIGS. 9-13 illustrate, by way of example, various embodiments of anelectrode assembly for placement in the lymphatic vessel to allow forthe neural stimulation. The electrode assembly includes one or moreelectrode bases. One or more stimulation electrodes are incorporatedonto and/or integrated with each of the one or more electrode bases. Inone embodiment, the one or more electrode bases each are formed asportion of a lead such as lead 112. In one specific embodiment, anelectrode base is formed at distal end 116 of lead 112, and stimulationelectrodes 120 and 122 are on that electrode base. In another specificembodiment, one or more electrode bases are formed in elongate lead body118 of lead 112. In another embodiment, electrode bases are formed atdistal end 116 and elongate lead body 118 of lead 112 to provide fordelivery of the neural stimulation pulses to multiple target regions.

FIG. 9 is an illustration of a lymphatic vessel 905 and a target region907 in their natural state. Target region 907 is a region in the nervoussystem to which the neural stimulation pulses are delivered. Asillustrated in FIG. 9, lymphatic vessel 905 and target region 907 arenot in direct contact, or not constantly in direct contact, with eachother in their natural state. Electrode assemblies illustrated in FIGS.10-13 each cause and maintain a substantially constant and directcontact between lymphatic vessel 905 and target region 907 bysubstantially altering the natural path of lymphatic vessel 905. Such asubstantially constant and direct contact allows for a reliable deliveryof neural stimulation pulses from one or more electrodes in lymphaticvessel 905 to target region 907. In various embodiments, lymphaticvessel 905 represents one of the thoracic duct, a vessel branching fromthe thoracic duct, or any lymphatic vessel suitable for placement of theone or more electrodes for the delivery of the neural stimulationpulses.

FIG. 10 is an illustration of an embodiment of an electrode assemblyincluding an electrode base 1021 configured to be implanted in lymphaticvessel 905 and a stimulation electrode 1020 on electrode base 1021.Electrode base 1021 has an elongate shape and includes a bias configuredto cause a portion of lymphatic vessel 905 to substantially alter itsnatural path to contact target region 907. The bias also allowselectrode 1020 to be in contact with the inner wall of lymphatic vessel905 for delivering the neural stimulation pulses to target region 907.Electrode base 1021 has a stiffness allowing for stabilizing theposition of stimulation electrode 1020 in lymphatic vessel 905 andmaintaining the contact between the portion of lymphatic vessel 905 andtarget region 907 after implantation. In one embodiment, electrode base1021 is in a helical form. In one embodiment, electrode base 1021includes an elongate body having shape memory characteristics such thatit returns to its preformed shape after the implantation procedureduring which a stylet or guide wire may be used. The shape memorycharacteristics are provided by using a shape memory polymer such aspolyether polyurethane or a shape memory metal. In one embodiment, theelectrode assembly is coupled to implantable medical device 110 via alead such as lead 112. In a specific embodiment, electrode base 1021 isformed at distal end 116 of lead 112, with stimulation electrode 1020being stimulation electrode 120. In other specific embodiments, two ormore stimulation electrodes are incorporated into electrode base 1021.

FIG. 11 is an illustration of an embodiment of another electrodeassembly including an electrode base 1121 configured to be implanted inlymphatic vessel 905 and stimulation electrodes 1120 and 1122, both onelectrode base 1121. Electrode base 1121 has an elongate shape andincludes a bias configured to cause a portion of lymphatic vessel 905 tosubstantially alter its natural path to contact target region 907. Thebias also allows electrodes 1120 and 1122 to be in contact with theinner wall of lymphatic vessel 905 for delivering the neural stimulationpulses to target region 907 using either or both of electrodes 1120 and1122. Electrode base 1121 has the stiffness allowing for stabilizing thepositions of stimulation electrodes 1120 and 1122 in lymphatic vessel905 and maintaining the contact between the portion of lymphatic vessel905 and target region 907 after implantation. In one embodiment,electrode base 1121 is in a helical form. In one embodiment, electrodebase 1121 includes an elongate body having shape memory characteristicssuch that it returns to its preformed shape after the implantationprocedure during which a stylet or guide wire may be used. The shapememory characteristics are provided by using a shape memory polymer suchas polyether polyurethane or a shape memory metal. In one embodiment,the electrode assembly is coupled to implantable medical device 110 viaa lead such as lead 112. In a specific embodiment, electrode base 1121is formed at distal end 116 of lead 112, with stimulation electrodes1120 and 1122 being stimulation electrodes 120 and 122. In otherspecific embodiments, one stimulation electrode, or three or morestimulation electrodes, are incorporated into electrode base 1121.

FIG. 12 is an illustration of an embodiment of another electrodeassembly including an electrode base 1121 with stimulation electrodes1120 and 1122 and another electrode base 1221 with stimulationelectrodes 1220 and 1222. Electrode bases 1121 and 1221 are bothconfigured to be implanted in lymphatic vessel 905. Electrode bases 1121has the elongate shape and includes the bias configured to cause aportion of lymphatic vessel 905 to substantially alter its natural pathto contact target region 907. The bias also allows electrodes 1120 and1122 to be in contact with the inner wall of lymphatic vessel 905 fordelivering neural stimulation pulses to target region 907 using eitheror both of electrodes 1120 and 1122. Electrode bases 1221 has anelongate shape and includes a bias configured to cause a portion oflymphatic vessel 905 to substantially alter its natural path to contacta target region 1207. The bias also allows electrodes 1220 and 1222 tobe in contact with the inner wall of lymphatic vessel 905 for deliveringneural stimulation pulses to target region 1207 using either or both ofelectrodes 1220 and 1222. Electrode bases 1121 and 1221 each have astiffness allowing for stabilizing the positions of the stimulationelectrodes in lymphatic vessel 905 and maintaining the contact betweenthe portion of lymphatic vessel 905 and target region 907 afterimplantation. In one embodiment, electrode bases 1121 and 1221 are eachin a helical form. In one embodiment, electrode bases 1121 and 1221 eachinclude an elongate body having shape memory characteristics such thatit returns to its preformed shape after the implantation procedureduring which a stylet or guide wire may be used. The shape memorycharacteristics are provided by using a shape memory polymer such aspolyether polyurethane or a shape memory metal. In one embodiment, theelectrode assembly is coupled to implantable medical device 110 via alead such as lead 112. In a specific embodiment, electrode base 1121 isformed at distal end 116 of lead 112, with stimulation electrodes 1120and 1122 being stimulation electrodes 120 and 122, and electrode base1221 is formed in elongate lead body 118 of lead 112. In other specificembodiments, one stimulation electrode, or three or more stimulationelectrodes, are incorporated into each of electrode bases 1121 and 1221.

FIG. 13 is an illustration of an embodiment of another electrodeassembly including an electrode base 1321 and a stimulation electrode1320. Electrode base 1321 is expandable. After being expanded, electrodebase 1321 causes a portion of lymphatic vessel 905 to substantiallyexpand to contact target region 907. The expansion of electrode base1321 also allows electrode 1320 to be in stable contact with the innerwall of lymphatic vessel 905 for delivering neural stimulation pulses totarget region 907. In one embodiment, electrode base 1321 includes astent that is expanded in the lymphatic vessel to maintain patency ofthe vessel. In one embodiment, stimulation electrode 1320 isincorporated into the stent. In another embodiment, the stent is made ofmetal and functions as stimulation electrode 1320. In anotherembodiment, stimulation electrode 1320 is integrated into the stent tobe a portion of its structure. The stent also stabilize the position ofstimulation electrode 1320 in lymphatic vessel 905 and preventsobstruction of the lymphatic flow. In one embodiment, the electrodeassembly is coupled to implantable medical device 110 via a lead such aslead 112. In a specific embodiment, the stent is incorporated intodistal end 116 of lead 112. In another embodiment, the stent isincorporated into elongate lead body 118 of lead 112. In anotherembodiment, two or more stents are incorporated into elongate lead body118 and/or distal end 116 of lead 112.

It is to be understood that the above detailed description is intendedto be illustrative, and not restrictive. Other embodiments will beapparent to those of skill in the art upon reading and understanding theabove description. The scope of the invention should, therefore, bedetermined with reference to the appended claims, along with the fullscope of equivalents to which such claims are entitled.

1. A system for delivering neural stimulation to a target region in abody having lymphatic vessels, the system comprising: a first electrodeassembly including a first electrode base configured to be implantedinto one of the lymphatic vessels and a first stimulation electrode onthe first electrode base, the first electrode base configured to cause aportion of the one of the lymphatic vessels to substantially alter itsnatural path to contact the target region and maintain the contactbetween the portion of the one of the lymphatic vessels and the targetregion after an implantation of the first electrode assembly; and animplantable medical device including a neural stimulation circuitadapted to deliver neural stimulation pulses through the firststimulation electrode.
 2. The system of claim 1, wherein the firstelectrode base comprises an elongate electrode base including one ormore biases each configured to cause the portion of the one of thelymphatic vessels to substantially alter its natural path to contact thetarget region, the elongate electrode base having a stiffness allowingfor maintaining the contact between the portion of the one of thelymphatic vessels and the target region after the implantation of thefirst electrode assembly.
 3. The system of claim 1, wherein the firstelectrode base comprises an expandable electrode base configured tocause the portion of the one of the lymphatic vessels to substantiallyalter its natural path to contact the target region, after beingexpanded.
 4. The system of claim 3, wherein the expandable electrodebase comprises a stent, and the first electrode is incorporated into orintegrated with the stent.
 5. The system of claim 1, further comprisinga first implantable lead having a first distal end, a first proximal endconfigured to be connected to the implantable medical device, and afirst elongate lead body between the first distal end and the firstproximal end, and wherein the first electrode assembly is incorporatedinto the first implantable lead.
 6. The system of claim 5, wherein thefirst electrode assembly is incorporated into the first distal end. 7.The system of claim 5, wherein the first electrode assembly isincorporated into the first elongate lead body.
 8. The system of claim5, wherein the first electrode base further comprises a secondstimulation electrode, and the neural stimulation circuit is adapted todeliver the neural stimulation pulses through the first stimulationelectrode and the second stimulation electrode.
 9. The system of claim5, further comprising a second stimulation electrode configured to beplaced in a location external to the lymphatic vessels, and wherein theneural stimulation circuit is adapted to deliver the neural stimulationpulses through the first stimulation electrode and the secondstimulation electrode.
 10. The system of claim 9, further comprising asecond implantable lead configured to be subcutaneously implanted, thesecond implantable lead having a second distal end including the secondstimulation electrode, a second proximal end configured to be connectedto the implantable medical device, and a second elongate lead bodybetween the distal end and the proximal end.
 11. The system of claim 9,wherein the second stimulation electrode is incorporated onto theimplantable medical device.
 12. The system of claim 5, comprising aphysiological sensor adapted to sense a physiological signal, andwherein the implantable medical device comprises: a sensing circuit,coupled to the physiological sensor, to process the physiologicalsignal; and an implant control circuit adapted to control the deliveryof the neural stimulation pulses using the physiological signal.
 13. Thesystem of claim 12, wherein the physiological sensor comprises an neuralsensing electrode configured to sense a neural signal, the sensingcircuit comprises a neural sensing circuit to process the neural signal,and the implant control circuit is adapted to control the delivery ofthe neural stimulation pulses using the processed neural signal.
 14. Thesystem of claim 13, wherein the neural sensing electrode is the firststimulation electrode.
 15. The system of claim 13, wherein the implantcontrol circuit comprises a closed-loop controller adapted to providefeedback control of the delivery of the neural stimulation pulses usingthe sensed neural signal as an input signal.
 16. The system of claim 5,wherein the implantable medical device comprises an implant controlcircuit adapted to control the delivery of the neural stimulation pulsesusing a plurality of stimulation parameters, the implant control circuitincluding: a parameter storage circuit to store values of the pluralityof stimulation parameters; and a parameter receiver to receive one ormore programmed values of the plurality of stimulation parameters and toupdate the parameter storage circuit with the received one or moreprogrammed values of the plurality of stimulation parameters.
 17. Thesystem of claim 16, wherein the implantable medical device comprises animplant telemetry circuit to receive the one or more programmed valuesof the plurality of stimulation parameters.
 18. The system of claim 17,further comprising an external system communicatively coupled to theimplantable medical device, the external system including: a user inputdevice adapted to allow programming of the one or more programmed valuesof the parameters; and an external telemetry circuit to transmit the oneor more programmed values of the plurality of stimulation parameters tothe implantable medical device.
 19. A method for delivering neuralstimulation to a body having lymphatic vessels including a thoracicduct, the method comprising: delivering neural stimulation pulses froman implantable medical device to at least a first stimulation electrodeplaced in one of the lymphatic vessels.
 20. The method of claim 19,further comprising altering a natural path of the one of the lymphaticvessels to cause a portion of the one of the lymphatic vessels tocontact a target region to which the neural stimulation are deliveredusing an electrode base configured to be implanted in the one of thelymphatic vessels, and wherein the first stimulation electrode isincorporated into or integrated with the electrode base.
 21. The methodof claim 19, wherein delivering the neural stimulation pulses comprisesdelivering the neural stimulation pulses through a stimulation electrodeplaced in the thoracic duct.
 22. The method of claim 19, whereindelivering the neural stimulation pulses comprises delivering the neuralstimulation pulses through a stimulation electrode placed in one of thevessels branching from the thoracic duct.
 23. The method of claim 19,wherein delivering the neural stimulation pulses comprises deliveringthe neural stimulation pulses through the first stimulation electrodeand a second stimulation electrode placed in the one of the lymphaticvessels.
 24. The method of claim 19, wherein delivering the neuralstimulation pulses comprises delivering the neural stimulation pulsesthrough the first stimulation electrode and a second stimulationelectrode placed in a location in the body external the lymphaticvessels.
 25. The method of claim 19, further comprising: sensing one ormore physiological signals; and controlling the delivery of the neuralstimulation pulses using the one or more physiological signals.
 26. Themethod of claim 25, wherein sensing the one or more physiologicalsignals comprises sensing a neural signal using the first stimulationelectrode, and controlling the delivery of the neural stimulation pulsescomprises controlling the delivery of the neural stimulation pulsesusing the neural signal.
 27. The method of claim 19, further comprising:controlling the delivery of the neural stimulation pulses using aplurality of stimulation parameters; receiving one or more values of theplurality of stimulation parameters; and storing the received one ormore values of the plurality of the stimulation parameters.
 28. Themethod of claim 27, further comprising programming one or more values ofthe stimulation parameters according to a target to which the neuralstimulation pulses are delivered, the target including one or morecomponent of a nervous system.
 29. The method of claim 28, whereindelivering the neural stimulation pulses comprises delivering the neuralstimulation pulses to a parasympathetic nerve.
 30. The method of claim29, wherein delivering the neural stimulation pulses comprisesdelivering the neural stimulation pulses to a vagus nerve.
 31. Themethod of claim 28, wherein delivering the neural stimulation pulsescomprises delivering the neural stimulation pulses to a sympatheticnerve.
 32. The method of claim 28, wherein delivering the neuralstimulation pulses comprises delivering the neural stimulation pulses toa spinal cord.
 33. The method of claim 28, wherein delivering the neuralstimulation pulses comprises delivering the neural stimulation pulses tobaroreceptors.